Denture stomatitis (DS), usually caused by Candida infection, is one of the common denture-related complications in patients wearing dentures. Clove and cinnamon oils have been acknowledged for their anti-inflammatory, antimicrobial activity, and antifungal effects in the oral cavity. The aim of this study, therefore, was to prepare clove/cinnamon oils-loaded emulgel and to assess its efficacy in treating Candida albicans-associated denture stomatitis. Central composite design was adopted to formulate and optimize clove/cinnamon extracts-loaded emulgel. The formulated preparations were assessed for their physical appearance, particle size, viscosity, spreadability, and in-vitro drug release. In addition, in-vivo therapeutic experiments were conducted on 42 patients with denture stomatitis. The prepared emulgel formulations showed good physical characteristics with efficient drug release within 3 h. In addition, in-vivo antifungal studies revealed that the optimized formula significantly (p < 0.001) reduced Candida colony counts from the denture surface, compared to commercially available gel (240.38  27.20 vs. 398.19  66.73 CFU/mL, respectively). Furthermore, the optimized formula and succeeded in alleviating denture stomatitis-related inflammation with a better clinical cure rate compared to commercially available gel Collectively, herbal extracts-loaded emulgel might be considered an evolution of polyherbal formulations and might represent a promising alternative to the existing allopathic drugs for the treatment of denture stomatitis, with better taste acceptability and no side effects.